A significant increase was found in BACE-1 concentration and activity in the CSF of MCI subjects compared with healthy controls; subjects with the ApoE e4 risk allele were found to have the highest concentrations. BACE-1 may have added value in early detection, prediction, and biological activity of AD.101 Isoprostanes are also being studied as candidate markers of lipid peroxidation. An Inhibitors,research,lifescience,medical increase was found in the CSF of MCI subjects compared with controls, and levels also increased over time, With

regards to their diagnostic precision, the CSF markers isoprostanes and p-tau performed better than memory tests. The isoprostanes even improved the results obtained using hippocampal volumetry Inhibitors,research,lifescience,medical to distinguish between the groups.102 However, due to the very demanding analysis SB939 nmr method, isoprostanes should still be regarded as a merely scientific approach.

This also holds true for the role of apop tosis, oxidative stress, and mitochondrial dysfunction in lymphocytes as potential biomarkers for Alzheimer’s disease which are currently under investigation.103 Biomarkers Inhibitors,research,lifescience,medical derived from plasma and serum The efforts to discover and develop diagnostic biomarkers for AD in peripheral blood, plasma, or serum has to date not led to any core feasible candidate markers that are even close to the diagnostic accuracy achieved by CSF biomarkers. The best-studied candidate biomarker in plasma so far is Aβ, but the findings are contradictory. Some groups have reported high concentrations in plasma of either Aβ42 or Aβ40 in AD, although with a broad overlap Inhibitors,research,lifescience,medical between patients and controls, whereas most groups find no change.104

Some studies have also reported high plasma Aβ42 (but not Aβ40) in nondemented elderly people who later developed either progressive cognitive decline or AD.105,106 Contrary to these data, van Oijen and colleagues Inhibitors,research,lifescience,medical recently reported an association between high Aβ40, low Aβ42, and risk of dementia,107 a result that is in general agreement with the findings of Graff-Radford and colleagues,108 who observed a weak association between low plasma Aβ42/Aβ40 ratio and risk of future MCI or AD in a healthy, elderly population. Apart from disease-related factors, the opposing results may be due to the fact that Aβ42 is methodologically difficult to measure reliably in plasma. The peptide is very hydrophobic aminophylline and binds, not only to certain test tube walls, but also to several plasma proteins, including albumin, a2-macroglobulin, lipoproteins, and complement factors.109 Additionally, it is unclear what effect Aβ oligomerization has on Aβ concentrations in plasma measured by immunochemical assays. Both homo- and heterotypic protein interactions could mask Aβ epitopes, resulting in the measurement of only a fraction of Aβ.